Using the isolated perfused spleen of the cat, studies of the effects of alpha-adrenergic blockers and nerve stimulation on H3- norepinephrine uptake and metabolism will be conducted. An attempt will be made to characterize more fully the axonal membrane amine uptake system and to determine the mechanism by which alpha-adrenergic blocking agents inhibit norepinephrine uptake. Studies on the influence of extravesicular, neuronal norepinephrine on the uptake of H3- norepinephrine will also be performed. The properties of the catecholamine uptake and storage mechanisms after prolonged stimulation or inactivity of the adrenergic nervous system will be examined. The synthesis and turnover of storage vesicle adenine nucleotides and the effect of nerve stimulation on the synthesis, release and turnover of this component of the storage vesicle will be determined. Pharmacological interactions between adenine nucleotides and catecholamines will be studied in the isolated perfused spleen. A systematic analysis of the factors which significantly influence the maintenance of neurotransmitter stores during and after prolonged stimulation of the nerve to the isolated perfused spleen will be made. The role of transaminases and alpha-keto acids in regulating tyrosine and dopa metabolism and norepinephrine synthesis in brain and in peripheral adrenergic nervous tissue will be evaluated. The mechanisms by which amphetamine modifies tyrosine hydroxylase activity in intact, isolated tissues will be investigated.